We wish to characterize the mechanisms for responsible for focal segmental glomerulosclerosis (FSGS) and use these findings to devise more effective therapy; we are particularly interested in HIV- associated FSGS.We have hypothesized that HIV accessory proteins (Vpr, Vpu, and Vif) mediate renal injury, leading to the histologic pattern of focal segmental glomerulosclerosis. We have established transgenic lines which will express Vpr under the control of a tetracycline inducible promoter.We have collected blood and prepared immortalized B cell lines as a source of DNA from approximately 160 African-American patients with FSGS and a control group 210 African Americans infected with HIV but without renal disease, with the help of collaborators from 12 medical centers around the country. We have initiated candidate gene analysis and plan a genome scan within the next year.We have submitted a protocol to test two agents, pirfenidone and probucol, in 20 patients with idiopathic or HIV-associated FSGS using a randomized block design, with each drug used as a single agent for 4 months and with proteinuria as the primary endp - focal segmental glomerulosclerosis, kidney disease, African American, HIV-1, Vpu, Vpr, Vif - Human Subjects